Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Disulfide Bond as a Structural Determinant of Prion Protein Membrane Insertion

  • Shin, Jae Yoon (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Shin, Jae Il (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Kim, Jun Seob (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Yang, Yoo Soo (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Shin, Yeon-Kyun (Department of Biochemistry and Biophysics, Iowa State University) ;
  • Kim, Kyeong Kyu (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, and Sungkyunkwan University School of Medicine) ;
  • Lee, Sangho (Department of Biological Science, Sungkyunkwan University) ;
  • Kweon, Dae-Hyuk (Department of Genetic Engineering, Sungkyunkwan University)
  • Received : 2009.02.23
  • Accepted : 2009.04.22
  • Published : 2009.06.30
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Abstract

Conversion of the normal soluble form of prion protein, PrP ($PrP^C$), to proteinase K-resistant form ($PrP^{Sc}$) is a common molecular etiology of prion diseases. Proteinase K-resistance is attributed to a drastic conformational change from ${\alpha}$-helix to ${\beta}$-sheet and subsequent fibril formation. Compelling evidence suggests that membranes play a role in the conformational conversion of PrP. However, biophysical mechanisms underlying the conformational changes of PrP and membrane binding are still elusive. Recently, we demonstrated that the putative transmembrane domain (TMD; residues 111-135) of Syrian hamster PrP penetrates into the membrane upon the reduction of the conserved disulfide bond of PrP. To understand the mechanism underlying the membrane insertion of the TMD, here we explored changes in conformation and membrane binding abilities of PrP using wild type and cysteine-free mutant. We show that the reduction of the disulfide bond of PrP removes motional restriction of the TMD, which might, in turn, expose the TMD into solvent. The released TMD then penetrates into the membrane. We suggest that the disulfide bond regulates the membrane binding mode of PrP by controlling the motional freedom of the TMD.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

References

  1. Baron, G.S., and Caughey, B. (2003). Effect of glycosylphosphatidylinositol anchor-dependent and -independent prion protein association with model raft membranes on conversion to the protease- resistant isoform. J. Biol. Chem. 278, 14883-14892 https://doi.org/10.1074/jbc.M210840200
  2. Castilla, J., Sa$\acute{a}$, P., Hetz, C., and Soto, C. (2005).In vitro generation of infectious scrapie prions. Cell 121, 195-206 https://doi.org/10.1016/j.cell.2005.02.011
  3. Critchley, P., Kazlauskaite, J., Eason, R., and Pinheiro, T.J. (2004). Binding of prion proteins to lipid membranes. Biochem. Biophys. Res. Commun.313, 559-567 https://doi.org/10.1016/j.bbrc.2003.12.004
  4. De Gioia, L., Selvaggini, C., Ghibaudi, E., Diomede, L., Bugiani, O., Forloni, G., Tagliavini, F., and Salmona, M. (1994). Conformational polymorphism of the amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein. J. Biol. Chem. 269, 7859-7862
  5. Deleault, N.R., Harris, B.T., Rees, J.R., and Supattapone, S. (2007). From the cover: formation of native prions from minimal compo-nents In vitro. Proc. Natl. Acad. Sci. USA 104, 9741-9746 https://doi.org/10.1073/pnas.0702662104
  6. Eftink, M.R., and Ghiron, C.A. (1981). Fluorescence quenching studies with proteins. Anal. Biochem. 114, 199-227 https://doi.org/10.1016/0003-2697(81)90474-7
  7. Fanucci, G.E., and Cafiso, D.S. (2006). Recent advances and applications of site-directed spin labeling. Curr. Opin. Struct. Biol. 16, 644-653 https://doi.org/10.1016/j.sbi.2006.08.008
  8. Forloni, G., Angeretti, N., Chiesa, R., Monzani, E., Salmona, M., Bugiani, O., and Tagliavini, F. (1993) Neurotoxicity of a prion protein fragment. Nature 362, 543-546 https://doi.org/10.1038/362543a0
  9. Hegde, R.S., Mastrianni, J.A., Scott, M.R., DeFea, K.A., Tremblay, P., Torchia, M., DeArmond, S.J., Prusiner, S.B., and Lingappa, V.R. (1998). A transmembrane form of the prion protein in neurodegenerative disease. Science 279, 827-834 https://doi.org/10.1126/science.279.5352.827
  10. Hegde, R.S., Tremblay, P., Groth, D., DeArmond, S.J., Prusiner, S.B., and Lingappa, V.R. (1999). Transmissible and geneti prion diseases share a common pathway of neurodegeneration. Nature 402, 822 https://doi.org/10.1038/45574
  11. Horiuchi, M., and Caughey, B. (1999). Prion protein interconversions and the transmissible spongiform encephalopathies. Structure 7, R231-240 https://doi.org/10.1016/S0969-2126(00)80049-0
  12. Hubbell, W.L., McHaourab, H.S., Altenbach, C., and Lietzow, M.A. (1996). Watching proteins move using site-directed spin labeling. Structure 4, 779-783 https://doi.org/10.1016/S0969-2126(96)00085-8
  13. Hubbell, W.L., Cafiso, D.S., and Altenbach, C. (2000). Identifying conformational changes with site-directed spin labeling. Nat. Struct. Biol. 7, 735-739 https://doi.org/10.1038/78956
  14. Jackson, G.S. (1999). Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations. Science 283, 1935 https://doi.org/10.1126/science.283.5409.1935
  15. James, T.L., Liu, H., Ulyanov, N.B., Farr-Jones, S., Zhang, H., Donne, D.G., Kaneko, K., Groth, D., Mehlhorn, I., Prusiner, S.B., et al. (1997). Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform. Proc. Natl. Acad. Sci. USA 94, 10086-10091 https://doi.org/10.1073/pnas.94.19.10086
  16. Kazlauskaite, J., and Pinheiro, T.J. (2005). Aggregation and fibrillization of prions in lipid membranes. Biochem. Soc. Symp. 72, 211-222 https://doi.org/10.1042/bss0720211
  17. Kazlauskaite, J., Sanghera, N., Sylvester, I., V$\acute{e}$nien-Bryan, C., and Pinheiro, T.J. (2003). Structural changes of the prion protein in lipid membranes leading to aggregation and fibrillization. Biochemistry 42, 3295-3304 https://doi.org/10.1021/bi026872q
  18. Knaus, K.J., Morillas, M., Swietnicki, W., Malone, M., Surewicz, W.K., and Yee, V.C. (2001). Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat. Struct. Biol. 8, 770-774 https://doi.org/10.1038/nsb0901-770
  19. Kocisko, D.A., Come, J.H., Priola, S.A., Chesebro, B., Raymond, G.J., Lansbury, P.T., and Caughey, B. (1994). Cell-free formation of protease-resistant prion protein. Nature 370, 471-474 https://doi.org/10.1038/370471a0
  20. Kweon, D.H., Shin, Y.K., Shin, J.Y., Lee, J.H., Lee, J.B., Seo, J.H., and Kim, Y.S. (2006). Membrane topology of helix 0 of the Epsin N-terminal homology domain. Mol. Cells 21, 428-435
  21. Legname, G., Baskakov, I.V., Nguyen, H.O., Riesner, D., Cohen, F.E., DeArmond, S.J., and Prusiner, S.B. (2004). Synthetic mammalian prions. Science 305, 673-676 https://doi.org/10.1126/science.1100195
  22. Lin, M.C., Mirzabekov, T., and Kagan, B.L. (1997). Channel formation by a neurotoxic prion protein fragment. J. Biol. Chem. 272, 44-47 https://doi.org/10.1074/jbc.272.1.44
  23. L$\acute{o}$pez Garc$\acute{i}$a, F., Zahn, R., Riek, R., and W$\ddot{u}$thrich, K. (2000). NMR structure of the bovine prion protein. Proc. Natl. Acad. Sci. USA 97, 8334-8339 https://doi.org/10.1073/pnas.97.15.8334
  24. Maiti, N.R., and Surewicz, W.K. (2001). The role of disulfide bridge in the folding and stability of the recombinant human prion protein. J. Biol. Chem. 276, 2427-2431 https://doi.org/10.1074/jbc.M007862200
  25. McHaourab, H.S., Kalai, T., Hideg, K., and Hubbell, W.L. (1999). Motion of spin-labeled side chains in T4 lysozyme: effect of side chain structure. Biochemistry 38, 2947-2955 https://doi.org/10.1021/bi9826310
  26. Mehlhorn, I., Groth, D., Stockel, J., Moffat, B., Reilly, D., Yansura, D., Willett, W.S., Baldwin, M., Fletterick, R., Cohen, F.E., et al. (1996). High-level expression and characterization of a purified 142-residue polypeptide of the prion protein. Biochemistry 35, 5528-5537 https://doi.org/10.1021/bi952965e
  27. Morillas, M., Swietnicki, W., Gambetti, P., and Surewicz, W.K. (1999). Membrane environment alters the conformational structure of the recombinant human prion protein. J. Biol. Chem 274, 36859-36865 https://doi.org/10.1074/jbc.274.52.36859
  28. Muramoto, T., Scott, M., Cohen, F.E., and Prusiner, S.B. (1996). Recombinant scrapie-like prion protein of 106 amino acids is soluble. Proc. Natl. Acad. Sci. USA 93, 15457-15462 https://doi.org/10.1073/pnas.93.26.15457
  29. Pinheiro, T.J. (2006). The role of rafts in the fibrillization and aggregation of prions. Chem. Phys. Lipids 141, 66-71 https://doi.org/10.1016/j.chemphyslip.2006.02.022
  30. Prusiner, S.B. (1998). Prions. Proc. Natl. Acad. Sci. USA 95, 13363-13383 https://doi.org/10.1073/pnas.95.23.13363
  31. Re, F., Sesana, S., Barbiroli, A., Bonomi, F., Cazzaniga, E., Lonati, E., Bulbarelli, A., and Masserini, M. (2008). Prion protein structure is affected by pH-dependent interaction with membranes: a study in a model system. FEBS Lett. 582, 215-220 https://doi.org/10.1016/j.febslet.2007.12.003
  32. Riek, R., Hornemann, S., Wider, G., Billeter, M., Glockshuber, R., and W$\ddot{u}$thrich, K. (1996). NMR structure of the mouse prion protein domain PrP(121-321). Nature 382, 180-182 https://doi.org/10.1038/382180a0
  33. Sanghera, N., and Pinheiro, T.J. (2002). Binding of prion protein to lipid membranes and implications for prion conversion. J. Mol. Biol. 315, 1241-1256 https://doi.org/10.1006/jmbi.2001.5322
  34. Shin, J.I., Shin, J.Y., Kim, J.S., Yang, Y.S., Shin, Y.K., and Kweon, D.H. (2008). Deep membrane insertion of prion protein upon reduction of disulfide bond. Biochem. Biophys. Res. Commun. 377, 995-1000 https://doi.org/10.1016/j.bbrc.2008.10.095
  35. St$\ddot{o}$hr, J., Weinmann, N., Wille, H., Kaimann, T., Nagel-Steger, L., Birkmann, E., Panza, G., Prusiner, S.B., Eigen, M., and Riesner, D. (2008). Mechanisms of prion protein assembly into amyloid. Proc. Natl. Acad. Sci. USA 105, 2409-2414 https://doi.org/10.1073/pnas.0712036105
  36. Swietnicki, W., Petersen, R., Gambetti, P., and Surewicz, W.K. (1997). pH-dependent stability and conformation of the recombinant human prion protein PrP(90-231). J. Biol. Chem. 272, 27517-27520 https://doi.org/10.1074/jbc.272.44.27517
  37. Turk, E., Teplow, D.B., Hood, L.E., and Prusiner, S.B. (1988). Purification and properties of the cellular and scrapie hamster prion proteins. Eur. J. Biochem. 176, 21-30 https://doi.org/10.1111/j.1432-1033.1988.tb14246.x
  38. Wang, X., Wang, F., Arterburn, L., Wollmann, R., and Ma, J. (2006). The interaction between cytoplasmic prion protein and the hydrophobic lipid core of membrane correlates with neurotoxicity. J. Biol. Chem. 281, 13559-13565 https://doi.org/10.1074/jbc.M512306200
  39. Welker, E., Wedemeyer, W.J., Narayan, M., and Scheraga, H.A. (2001). Coupling of conformational folding and disulfide-bond reactions in oxidative folding of proteins. Biochemistry 40, 9059-9064 https://doi.org/10.1021/bi010409g
  40. Welker, E., Raymond, L.D., Scheraga, H.A., and Caughey, B. (2002). Intramolecular versus intermolecular disulfide bonds in prion proteins. J. Biol. Chem. 277, 33477-33481 https://doi.org/10.1074/jbc.M204273200
  41. Zahn, R., Liu, A., L$\ddot{u}$hrs, T., Riek, R., von Schroetter, C., L$\acute{o}$pez Garc$\acute{i}$a, F., Billeter, M., Calzolai, L., Wider, G., and W$\ddot{u}$thrich, K. (2000). NMR solution structure of the human prion protein. Proc. Natl. Acad. Sci. USA 97, 145-150 https://doi.org/10.1073/pnas.97.1.145

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